Organic compounds are purified on a daily basis in uncounted numbers of research and commercial laboratories and plants around the world. Purification costs account for a significant fraction of the expenses for organic compounds developed and sold by chemical, pharmaceutical, and other industries. Chromatographic methods of purification are immensely important, yet they are also expensive and time consuming. Simpler but sometimes less effective methods are based on techniques of phase separation. Four phases are commonly used in standard laboratory separation methods: a gas phase, a solid phase, and two liquid phases--organic and aqueous. Among the phase separation techniques, liquid--liquid extractions play a time-honored role in the purification of organic compounds. These extractions are almost always conducted with an organic solvent and water. Most frequently, they are used to separate (that is, purify) organic compounds from inorganic compounds. A less frequent but still important application of organic-water extractions is an acid-base extraction.
It is not widely recognized by synthetic organic chemists that there is a "third liquid phase", the fluorocarbon (or "fluorous") phase, whose members are not miscible in either water or many organic solvents. See, for example, Hudlicky, M. "Chemistry of Organic Fluorine Compounds", Ellis Horwood: Chichester (1992). As used herein, the term "fluorous liquid phase" refers to a liquid phase comprising one or more solvents rich in carbon fluorine bonds. A fluorous liquid phase is substantially immiscible with an "organic phase" and forms a liquid-liquid biphasic mixture with an organic phase.
As used herein, the term "fluorous", when used in connection with an organic (carbon-containing) molecule, refers generally to an organic molecule having a domain or a portion thereof rich in carbon-fluorine bonds (for example, fluorocarbons, fluorohydrocarbons, fluorinated ethers and fluorinated amines) . Such portion or domain may comprise part of a fluorous compound or the entire fluorous compound. In general, compounds comprising a relatively high weight percentage of fluorine partition preferentially into the fluorous liquid phase in a fluorous/organic liquid biphasic mixture. See U.S. Pat. No. 5,463,082. As used herein, the terms "fluorocarbons" and "perfluorocarbons" include organic compounds in which all hydrogen atoms bonded to carbon atoms have been replaced by fluorine atoms. The terms "fluorohydrocarbons" and "hydrofluorocarbons" include organic compounds in which at least one hydrogen atom bonded to a carbon atom has been replaced by a fluorine atom. Saturated perfluorocarbon fluids have important applications in surface chemistry, biology, and engineering. Most organic compounds are completely or substantially insoluble in fluorocarbon fluids, and many organic solvents are immiscible therein, although this miscibility depends somewhat on the fluorous-organic pairing. Solvents like carbon tetrachloride, ether, and THF have the highest solubilities in fluorocarbon fluids, and pairings of fluorocarbon fluids with these solvents are either miscible or can be made miscible by slight warming.
There are a wide assortment of fluorocarbon fluids commercially available under trade names like "FLUTEC" and "FLUORINERT.TM.". These fluids are made industrially by chemical or electrochemical fluorination processes. Most of these are mixtures of fluorocarbons with similar boiling points (sometimes with small amounts of fluorinated ethers). These mixtures are roughly analogous to the "petroleum ether" solvents often used in organic chemistry. Fluorinated ethers and fluorinated amines are also commercially available.
Although rarely referred to as such, these fluorocarbon "fluids" are effectively solvents. The first application of fluorocarbon solvents in the area of 30 traditional organic synthesis appeared in 1993 when D. W. Zhu described a series of transesterification reactions in the Fluorinert fluid FC-77.TM. (a fluorocarbon mixture containing mostly isomers of C.sub.8 F.sub.18, bp 97.degree. C.). Zhu, D. W., Synthesis, 953-54 (1993). As illustrated in the following example, low boiling alcohols were replaced by high boiling ones, and phase separation was used at two stages. ##STR1## First, an "inverse Dean-Stark" trap was used to separate the low-boiling alcohol from the reaction mixture and thereby drive the equilibrium. Second, the product ester separated from the FC-77 on cooling. Another common fluorocarbon fluid is FC-72.TM., a mixture of C.sub.6 F.sub.14 isomers with a boiling point of 56.degree. C. FC-72 and FC-77 are commercially available from 3M.
Shortly after the work of Zhu, Horvath and Rabai described the synthesis of a "fluorous" phosphine ligand and used this to generate a rhodium catalyst for a standard hydroformylation reaction. Horvath, I. T. and Rabai, J., Science, 266, 72-75 (1994). See also U.S. Pat. No. 5,463,082; and Gladysz, J. A., Science, 266, 55 (1994). The hydroformylation was conducted in a liquid biphasic mixture of perfluoromethylcyclohexane (fluorous solubilizing solvent) and toluene (organic solubilizing solvent) under a CO/H.sub.2 atmosphere as illustrated below. ##STR2## The products were separated from the catalyst by separation of the two liquid reaction phases, and the recovered catalyst from the fluorinated phase was successfully reused in another hydroformylation.
The distinctive physiochemical properties of a fluorous liquid phase can be used advantageously to provide unexpected solvent effects including altered and improved product yields, reactivities and/or selectivities. Likewise, physiochemical differences between fluorous molecules and organic (that is, non-fluorous) molecules provide a valuable tool to effect separation.
It is, therefore, very desirable to develop additional fluorous reaction components, reaction systems, reaction schemes and separation schemes.